The hygiene hypothesis suggests that parasitic infection modulates host immune responses and decreases atopy, but other data suggest parasitic infections may induce allergic responsiveness. To examine the molecular, structural, and immunologic relationships between parasite-encoded antigens and major aeroallergen homologues, parasite- and allergen-specific IgE, IgG, and IgG in sera of filaria-infected and filarial-uninfected atopic individuals were compared using multiple sets of parasite antigens and their aero-allergen homologues. For all sets of antigens there was a high degree of identity at the amino acid level, and overlapping predicted 3-dimensional structures .We found that filarial infection increased the serological prevalence IgE directed against house dust mite and cockroach, but not against timothy grass that appeared to be related to the presence of structural similarity between the allergens and the helminth proteins. IgE ELISA confirmed that infected individuals had higher IgE prevalences to those recombinant allergens that had homologues in helminths. Mice infected with helminth Heligmosomoides polygyrus displayed increased levels of IgE and positive skin tests to allergens with homologues in the parasite. We have extended these findings to the level of the T cell. Using cells from individuals with filarial infection (with or without allergic disease) and those from uninfected individuals (with or without allergic disease), we have shown that parasite antigen (and their aero-allergen orthologues) drives a CD4+ IL-4/IL-13 dominated response in filarial infection that is augmented when the subject is also allergic when measured using multiparameter flow cytometry or multiplexed cytokine measurements.